GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:19734937

From GONUTS
Jump to: navigation, search
Citation

Blackburn, JS, Liu, I, Coon, CI and Brinckerhoff, CE (2009) A matrix metalloproteinase-1/protease activated receptor-1 signaling axis promotes melanoma invasion and metastasis. Oncogene 28:4237-48

Abstract

Hallmarks of malignant melanoma are its propensity to metastasize and its resistance to treatment, giving patients with advanced disease a poor prognosis. The transition of melanoma from non-invasive radial growth phase (RGP) to invasive and metastatically competent vertical growth phase (VGP) is a major step in tumor progression, yet the mechanisms governing this transformation are unknown. Matrix metalloproteinase-1 (MMP-1) is highly expressed by VGP melanomas, and is thought to contribute to melanoma progression by degrading type I collagen within the skin to facilitate melanoma invasion. Protease activated receptor-1 (PAR-1) is activated by MMP-1, and is also expressed by VGP melanomas. However, the effects of MMP-1 signaling through PAR-1 have not been examined in melanoma. Here, we demonstrate that an MMP-1/PAR-1 signaling axis exists in VGP melanoma, and is necessary for melanoma invasion. Introduction of MMP-1 into RGP melanoma cells induced gene expression associated with tumor progression and promoted invasion in vitro, and enhanced tumor growth and conferred metastatic capability in vivo. This study demonstrates that both the type I collagenase and PAR-1 activating functions of MMP-1 are required for melanoma progression, and suggests that MMP-1 may be a major contributor to the transformation of melanoma from non-invasive to malignant disease.

Links

PubMed PMC2788659 Online version:10.1038/onc.2009.272

Keywords

Animals; Cell Line, Tumor; Collagenases/metabolism; Disease Progression; Female; Gene Expression; Gene Expression Regulation, Neoplastic; Humans; Male; Matrix Metalloproteinase 1/metabolism; Matrix Metalloproteinase 1/physiology; Matrix Metalloproteinase 2/metabolism; Matrix Metalloproteinase 9/metabolism; Melanoma/pathology; Melanoma/physiopathology; Mice; Mice, Nude/metabolism; Mitogen-Activated Protein Kinase 3/metabolism; Neoplasm Invasiveness/physiopathology; Neovascularization, Pathologic; Osteonectin/metabolism; Receptor, PAR-1/physiology; Signal Transduction/physiology; Skin Neoplasms/pathology; Skin Neoplasms/physiopathology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:MMP1

GO:0016049: cell growth

ECO:0000314:

P

Figure 1A: Western blot analysis of MMP-1 protein production by normal melanocytes, Bowes RGP melanoma cells, and VMM12 VPG melanoma cells, and analysis PAR-1 protein expression by normal endothelial cells, Bowes and and VMM12. PAR-1 blots were re-probed for actin, as a loading control. MMP-1 band is 54kD, PAR-1 is 61kD, actin is 43kD

complete
CACAO 11744

Notes

See also

References

See Help:References for how to manage references in GONUTS.